Art of preparing 2-chloro-4-aminobenzene-1-arsinic acids.



{INITED s'ra rns PATENT cri ical LORENZ ACH, QEMANNHEIM-WALDHOF, ALBERTROTHMANN, or HEIDELBERG, AND HERMANN DIETERICH, or MANNHE'LM, GERMANY,ASSIGNORS 'ro FARBWERKE VORM. ,MEISTER LUoIUs & BRUENING.orriocHsT-oN-THEMAIN, GERMANY, A

. FIRM. I

No Drawing.

To all whom it may concern:

: amino Be it known that we, LORENZ AcH, ALBERT ROTIIMANN, and HERMANNDIETERICH, citizens of the German Empire, residing atMannheiin-lValdhof, Heidelberg, and Mannheim, Germany, respectively,have invented certain new and useful Improvements in the Art ofPreparing 2-Chloro-4-Aminobenzene- 1 ArsinicAcids; and we do herebydeclare the following tobe a full clear, and exact description of theinvention, such as will enable others skilled in the art to which itappertains to make'and use the same.

This invention relates to the art of preparing aromatic arseniccompounds and has more especially for its object thepreparation of2--chloi'obenzene-l-arsinic acids containing in p-position to thearsinic rest the group where R designates alkyl and R -any univalentradical such as hydrogen or alkyl.

.Of' the chlorin substitution productsof 'paininobenzene arsinic acidand its derivatives hitherto only such were known, WlllCXl contain thechlorin in: m-position to the These compounds differ from thenon-chlorinated bodies in possess arsinic group;

ing a greater-degree of toxical properties (cf. Bem'chte dew Deutschen(hemisc/zen Gescllschaft, Band i3, S. 531). For this reason they havenot found permanent use in therapeutics. \Ve have however made theremarkable discovery that'such in the amino group substitutedpaminobenzene arsinic acids which contain the chlorin in. oposition tothe arsinic group are much less poisonous for the organism of mammalsthan the corresponding non chlorinated arsinic acids, surpassing thesebodies on the other hand in their bactericidal action or microorganismssuch as for example the Spiroclimm. The preparation.of-these new,substancesis carried out by treating 3-chloro-1-aminobenzenes bearingone" or two substituents in the group and having the general where B,may denote'alkyl and R any Specification of Letters Patent.

univale'nt radical such ,as hydrogen or alkyl 1 p o I u with arsenic trichlorid, whereupon benzene-l-arsinic oxids are formed. By oxidation torinstance with hydrogen peroxid. potassium permanganate, mercuric oxid.etc. thesearsenic oxids readily can be converted into the correspondingarsinic acids. i

In the preparation of the new arsinic acids it is not necessary toisolate the intera d t 2-Cl-4-N -benzene 1 arsenic OXldS.

The two operations'of forming the arsenic Patented Oct. 12, 1915.Application filed January 26, 1914. Serial No. 81 1, 591.

oxids and of oxidizing these also can be carried out simultaneously. Thenew substances obtained by this process may likewise be used as startingmaterials for the preparation ofother therapeutical useful bodies. Thefollowing examples embodying wha we consider the preferred manner ofcarryins out the process comprised in our invention are given to fullydisclose the'same.

Example 1': 155 gm, m-chloro-dimethylanilin are heated together with 186gm.

arsenic trichlorid for 10 minutes onthe wa-' ter bath and are thenpoured into'500 cc. of water.

After solution has taken place 500.

cc. 10 times normal caustic soda solution are added whereupon thechlorodimethylaminobenzene arsenic oxid. whiclrfirst separates out goesinto solution; The solution is filtered and the unalteredm-chlorodimethylanilin removed by extraction with ether. The oxid isthenprecipitated froi'nthe alkaline solution in the form of a lightprecipitate by addition of hydrochloric acid until the reaction ofthesolution is weakly alkaline. with water and dried. It is a whitepowder melting at 88 C. It is readily soluble in j chloroform andbenzeneand also in dilute The precipitate 'is filtered ofi', washed,

acids, insoluble in alcohol and ether, Concent'rated hydrochloric acidconverts it into the hydrochloric acid salt of 2-chloro-4-dimethylainino-benzene-l-arsinic trichlorid, a substance which melts at116 C. and is readily soluble in alcohol acetone and water.

Aqueous alkaline solution reconverts this is changed into brown. Whenthe reaction body into the arsenic oxid. The conversion of2-chloro-l-dimethylamino-benzene-l-arsenlc oxid into the correspondingarsinic acid is carried out as follows.

10 gm. of the 2-chlorol-dimethylamino- 1 benzene-l-arsenic oXid aresuspended in 180 cc. of water and heated for a short time with 10 gm.ofred oxid of mercury. The solution is then made alkaline with carbonateof soda, filtered and the 2-chloro-l-dimethylamlno-benzene-l-arsinicacid is separated from the liquor by acidulating. Or one may dissolve 10gm. of the arsenic oxid in dilute caustic soda solution and add 6.2 gm.potassium permanganate in small portions. Afterfiltering the arsinicacid is precipitated with acetic acid. 2-chloro--l-dimethylamino-benzenearsinic acid is a white powder, melts above 300 C. and is insoluble incold water and alcohol. It dissolves more readily in hot alcohol and inconcentrated hydrochloric acid and glacial acetic acid. "In aqueousalkaline solution it is readily soluble.

Example 2; [41 gm. -m-chloro-monomethylanilin are heated together with37.2 gm. arsenic" trichlorid for l0 minutes on the water bath whilestirring. Thereby the temperature of the mixture is highly raised andafter a few minutes the greenish color isfinished the whole is pouredinto the 10 times quantity of water and caustic alkali is added untilalkaline reaction takes place. The unaltered base separated thereby isremoved by extracting with ether. By acidulating the strong alkalinesolution the 4- methylamino-2-chlorobenzene-l-arsenic oxid goes outinform of white colored flocks in the driedstate it forms a whiteamorphous powder melting at 120 and decomposing when heated above thispoint. It is readily soluble in acetone. chloroform andalcohol. Inordertoform the corresponding arsinic acid 2.31 gm. lmethylamino-2-chlorobenzene-l-arsenic oxid may be suspended in 5 cc. ofwater and then an aqueous solution of caustic soda may be added untilsolution has taken place. By adding a little surplus of diluted hydrogen.peroxid firstly a large. precipitate is formed which goes into solutionsoon after. Then the solution is acidulated and the product of thereaction separates; The thus obtained 4-methylamino-2-chlorobenzene-1-ars inic acid is a white powder, its melting point being 211 C. It isinsoluble in cold Water, acetone and chloroform, soluble in hot waterand alcohol.

What we claim and desire to secure b Letters Patent is:

1. The process of preparing aromatic arsenic compounds which consistsintreating chlorinated aromatic compounds conv2-- chloro lt-PK:

taming in m-position to the chlorin atom the group Ri N\R2 (where R,denotes alkyl and R a univalent radical) with arsenic trichlorid andoxidizing the resultant arsenic oxid.

2. The process of preparing aromatic arsenic compounds which consists intreating chlorinated benzenes containing in m-position to the chlorinatom the group /R1 N\R2 (where It, denotes alkyl and R a univalentradical) with arsenic trichlorid and oxidizing the resultant arsenicoxid.

3. The process of preparing aromatic arsenic compounds which consists intreatin chlorinated benzenes containing in mposition to the chlorin atomthe group N \H (where R, denotesalkyl) with arsenic trichlorid andoxidizing the resultant arsenic oxid.

4. The process of preparing aromatic arsenic compounds which consists intreating chlorinated benzenes containing in mposition to the chlorinatom the group K with arsenic trichlorid and oxidizing the resultant -N-2-Cl-benzene-1-arsenic oxid.

5. The process of preparing aromatic arsenic compounds which consists intreating chlorinated aromatic compounds containing in m-position to thechlorin atom the group \R2 (where R, denotes alkyl and R aunivalentradical) with arsenic trichlorid and oxidizing the resultant arsenicoXid with potassium permanganate in alkaline solution.

6. As a new class of compositions of matter aromatic compoundscontaining arsenic in the oxidized state andbearing in o-position to thearsenic rest a chlorin atom and in p-position the group R1 N R2, v(where R designates alkyl andrR a univalent radical), these substancesbeing solid and of white color and being soluble in hot alcohol andhaving great bactericidal action.

7 As a new class of chemical compounds bnzene 1 arsenic acids (where R,designates alkyl and B a univalent radical), these substances beingwhlte colored and solid, being soluble inhot Water, In testimony whereofwe hereunto afiix hot, alcohol and in aqueous solutions of causoursignatures in the presence of two Wittic alkalis and alkali carbonatesandhaving nesses. a great bactericidal action.

.5 8. As a new composition of inatter the 4- LORENZ ACH.

cHa' ALBERT ROTHMANN. N -2-chlorobenzene-l-arsenlc acid, this HERMANNDIETERICH.

substance being insoluble in cold Water, acetone and chloroform, solublein hot Water Witnesses:

10 and alcohol, being White colored and having: HANS HABZIG, a greatbactericidal action. SIS. BERGER.

